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Cysteine and mercapturate conjugates of oxidized dopamine are in human striatum but only the cysteine conjugate impedes dopamine trafficking in vitro and in vivo
Author(s) -
Sidell Kathrin R.,
Olson Sandra J.,
Ou Joyce J.,
Zhang Yueli,
Amarnath Ventkataraman,
Montine Thomas J.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00586.x
Subject(s) - dopaminergic , dopamine , striatum , neurodegeneration , chemistry , in vivo , nigrostriatal pathway , substantia nigra , pharmacology , biochemistry , medicine , endocrinology , biology , disease , microbiology and biotechnology
Recent results have suggested that some products of mercapturic acid pathway (MAP) metabolism of oxidized dopamine (DA) may contribute to mesostriatal dopaminergic neurodegeneration, and that at least one product, 5‐ S ‐cysteinyldopamine (Cys‐DA), is elevated in patients with advanced Parkinson's disease (PD) who have been treated with l ‐DOPA. Here we investigated MAP enzymes and products in the midbrain and striatum of control individuals and patients with dementia with Lewy bodies (DLB) who had less severe dopaminergic degeneration than PD patients and who were not treated with l ‐DOPA. We also determined the biological activity of MAP metabolites of oxidized DA using primary rat mesencephalic cultures, rat cerebral synaptosomes, and rat striatum in vivo microdialysis. Our results showed that the human mesostriatal dopaminergic pathway generates Cys‐DA but has limited enzymatic capacity for mercapturate formation, that striatal levels of MAP products of oxidized DA are not elevated in DLB patients compared with controls, and that Cys‐DA interferes with trafficking of DA in vitro and in vivo . These results indicate that while Cys‐DA is not increased in striatum of patients with mild dopaminergic neurodegeneration, it may interfere with uptake of DA in patients with advanced PD.